Effects of phosphorylation-related drugs on slow Ca²⁺ tail current in guinea-pig detrusor cells

In isolated guinea-pig detrusor cells, large conditioning depolarizations evoke slowly deactivating Ca²⁺ tail currents, considered to represent the second open state. The possible involvement of channel phosphorylation in this open state was examined. Application of isoprenaline caused a marginal increase in Ca²⁺ channel current evoked by simple depolarization, while forskolin did not. During application of either drug, slow-tail currents were never observed after simple depolarizations. The conditions necessary to induce slow-tail currents were not changed, even when cyclic AMP, ATP-γ-S (adenosine 5'-O-(3-thiotriphosphate)), GDP-β-S (guanosine 5'-O-(2-thiodiphosphate)) (in the pipette) or H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) (to the bathing solution) was applied. The frequent depolarization protocol, known to facilitate Ca²⁺ current via Ca²⁺ and cyclic AMP-dependent phosphorylation mechanism(s) in cardiac myocytes, did not induce slow-tail currents. These results suggest that the transition of Ca²⁺ channels to the second open state during large depolarization is not a result of (voltage-operated) channel phosphorylation itself. Possible underlying mechanisms are discussed. Copyright (C) 1999 Elsevier Science B.V.